The Open UniversitySkip to content

The Role of Calcium Signalling in Autophagy

Chehab, Tala (2018). The Role of Calcium Signalling in Autophagy. PhD thesis. The Open University.

Full text available as:
PDF (Version of Record) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (4MB) | Preview
Google Scholar: Look up in Google Scholar


Autophagy is a catabolic process that is important for degradation of cellular components, and for cell survival, and has also been associated with pathological disorders and tumour growth. Autophagy is a complex process; many factors and messengers converge to control steps along the autophagic pathway. Ca2+ has been proposed to regulate autophagy. However, Ca2+ has been proposed to be both pro- and anti-autophagic. To better understand how Ca2+ has these opposing effects, this study investigated in what ways particular sources of Ca2+, and the characteristics of Ca2+ signals impacted on autophagy.

The fundamental need for Ca2+ in the activation of autophagy was demonstrated by loading cells with an exogenous Ca2+ buffer, which prevented various stimuli from triggering autophagy.

Autophagy could be activated by inhibiting the transfer of Ca2+ from the endoplasmic reticulum to the mitochondrial matrix. This was achieved by expressing an enzyme that prevented Ca2+ release from inositol 1,4,5-trisphosphate receptors, inhibition of mitochondrial respiration, and knockdown of the mitochondrial Ca2+ uniporter. The triggering of autophagy under these conditions was due to reduced cellular ATP levels. These data suggest that Ca2+ signals arising from InsP3Rs suppress autophagy.

Additional studies used a well-characterised Ca2+ transport pathway to generate cellular Ca2+ signals, and examined their ability to trigger autophagy. This pathway, known as ‘store-operated Ca2+ entry’ (SOCE), was activated by depleting endoplasmic reticulum Ca2+ stores using inhibitors of sarco/endoplasmic reticulum ATPases (SERCA). It was found that sustained cellular Ca2+ signals arising via chronic inhibition of SERCA were pro-autophagic. The activation of autophagy absolutely required the presence of extracellular Ca2+, and was not due to cellular stress. Using pharmacological inhibition of various Ca2+-sensitive kinases, it was found that at least part of the autophagy that occurred during SOCE was due to activation of Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β, also known as CaMKK-2).

Item Type: Thesis (PhD)
Copyright Holders: 2017 The Author
Keywords: physiological effect of calcium; cellular signal transduction; cellular control mechanisms; cell interaction; cell death
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Item ID: 55091
Depositing User: Tala Chehab
Date Deposited: 22 May 2018 13:03
Last Modified: 16 Jan 2020 18:23
Share this page:

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU